Characterization of two common 5' polymorphisms in PEX1 and correlation to survival in PEX1 peroxisome biogenesis disorder patients.

[zellweger syndrome]

Mutations in PEX 1 are the most common primary cause of Zellweger syndrome . In addition to exonic mutations , deletions and splice site mutations two 5 ' polymorphisms at c .-137 and c .-53 with a potential influence on PEX 1 protein levels have been described in the 5 ' untranslated region (UTR ) of the PEX 1 gene .We used RACE and in silico promoter prediction analysis to study the 5 ' UTR of PEX 1 . We determined the distribution of PEX 1 5 ' polymorphisms in a cohort of 30 Zellweger syndrome patients by standard DNA sequencing . 5 ' polymorphisms were analysed in relation to the two most common mutations in PEX 1 and were incorporated into a novel genotype-phenotype analysis by correlation of three classes of PEX 1 mutations with patient survival .We provide evidence that the polymorphism 137 bp upstream of the ATG codon is not part of the UTR , rendering it a promoter polymorphism . We show that the first , but not the second most common PEX 1 mutation arose independently of a specific upstream polymorphic constellation . By genotype-phenotype analysis we identified patients with identical exonic mutation and identical 5 ' polymorphisms , but strongly differing survival .Our study suggests that two different types of PEX 1 5 ' polymorphisms have to be distinguished : a 5 ' UTR polymorphism at position c .-53 and a promoter polymorphism 137 bp upstream of the PEX 1 start codon . Our results indicate that the exonic PEX 1 mutation correlates with patient survival , but the two 5 ' polymorphisms analysed in this study do not have to be considered for diagnostic and /or prognostic purposes .

Diseases
Validation

Diseases presenting "upstream polymorphic constellation" symptom

zellweger syndrome

You can validate or delete this automatically detected symptom